Endothelial Cell Ion Channel Expression and Function in Arterioles and Resistance Arteries

Jackson, William F.

doi:10.1007/978-3-319-29635-7_1

Cited by 13 publications

(25 citation statements)

References 185 publications

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“…Although studied primarily in smooth muscle, endothelial K IR 2.1 channels are present in the endothelium of rodent resistance arteries and arterioles . In agreement with recent studies, our findings here using isolated cerebral endothelium indicate consistent hyperpolarization responses to 15 mmol·L −1 KCl (Figure A‐D).…”

Section: Discussionsupporting

confidence: 92%

“…12 Although studied primarily in smooth muscle, endothelial K IR 2.1 channels are present in the endothelium of rodent resistance arteries and arterioles. 42 In agreement with recent studies, 22,43 our findings here using isolated cerebral endothelium indicate consistent hyperpolarization responses to 15 mmolÁL À1 KCl (Figure 5A-D). Also, the apparent lack of endothelial K IR function in SEAs ( Figure 5E-H) is consistent with recent observations, whereby K IR channels play a dominant role in the smooth muscle layer in young (3-6 month) mice despite detectable mRNA expression of endothelial K IR 2.1 in both cell layers.…”

Section: Endothelial K Ca and K Ir Channelssupporting

confidence: 93%

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Electrical dynamics of isolated cerebral and skeletal muscle endothelial tubes: Differential roles of G‐protein‐coupled receptors and K⁺ channels

Hakim

Buchholz

Behringer

2018

Pharmacology Res & Perspec

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Electrical dynamics of freshly isolated cerebral endothelium have not been determined independently of perivascular nerves and smooth muscle. We tested the hypothesis that endothelium of cerebral and skeletal muscle arteries differentially utilizes purinergic and muscarinic signaling pathways to activate endothelium‐derived hyperpolarization. Changes in membrane potential (V m) were recorded in intact endothelial tubes freshly isolated from posterior cerebral and superior epigastric arteries of male and female C57BL/6 mice (age: 3‐8 months). V m was measured in response to activation of purinergic (P2Y) and muscarinic (M3) receptors in addition to small‐ and intermediate‐conductance Ca2+‐activated K+ (SKC a/IKC a) and inward rectifying K+ (KIR) channels using ATP (100 μmol·L−1), acetylcholine (ACh; 10 μmol·L−1), NS309 (0.01‐10 μmol·L−1), and 15 mmol·L−1 KCl, respectively. Intercellular coupling was demonstrated via transfer of propidium iodide dye and electrical current (±0.5‐3 nA) through gap junctions. With similarities observed across gender, peak hyperpolarization to ATP and ACh in skeletal muscle endothelial tubes was ~twofold and ~sevenfold higher, respectively, vs cerebral endothelial tubes, whereas responses to NS309 were similar (from resting V m ~−30 mV to maximum ~−80 mV). Hyperpolarization (~8 mV) occurred during 15 mmol·L−1 KCl treatment in cerebral but not skeletal muscle endothelial tubes. Despite weaker hyperpolarization during endothelial GPCR stimulation in cerebral vs skeletal muscle endothelium, the capability for robust SKC a/IKC a activity is preserved across brain and skeletal muscle. As vascular reactivity decreases with aging and cardiovascular disease, endothelial K+ channel activity may be calibrated to restore blood flow to respective organs regardless of gender.

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Section: Discussionsupporting

confidence: 92%

Section: Endothelial K Ca and K Ir Channelssupporting

confidence: 93%

Electrical dynamics of isolated cerebral and skeletal muscle endothelial tubes: Differential roles of G‐protein‐coupled receptors and K⁺ channels

Hakim

Buchholz

Behringer

2018

Pharmacology Res & Perspec

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“…However, we fully acknowledge that in intact resistance arteries and arterioles, SMCs are electrically coupled to underlying endothelial cells by myoendothelial gap junctions, and that endothelial cells also express their own cadre of ion channels (671). While it is known that hyperpolarization of endothelial cells (induced by opening of K Ca channels in these cells) can be transmitted to overlying SMCs (i.e., via EDHF), the impact of other endothelial cell ion channels on the regulation of membrane potential and function in the overlying SMC remains largely speculative, because the tools currently available to electrically uncouple these cell layers (mechanical denudation, available gap junction inhibitors, etc.)…”

Section: Conclusion and Remaining Questionsmentioning

confidence: 99%

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Tykocki

Boerman

Jackson

2017

Comprehensive Physiology

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270

347

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Vascular tone of resistance arteries and arterioles determines peripheral vascular resistance, contributing to the regulation of blood pressure and blood flow to, and within the body’s tissues and organs. Ion channels in the plasma membrane and endoplasmic reticulum of vascular smooth muscle cells (SMCs) in these blood vessels importantly contribute to the regulation of intracellular Ca2+ concentration, the primary determinant of SMC contractile activity and vascular tone. Ion channels provide the main source of activator Ca2+ that determines vascular tone, and strongly contribute to setting and regulating membrane potential, which, in turn, regulates the open-state-probability of voltage gated Ca2+ channels (VGCCs), the primary source of Ca2+ in resistance artery and arteriolar SMCs. Ion channel function is also modulated by vasoconstrictors and vasodilators, contributing to all aspects of the regulation of vascular tone. This review will focus on the physiology of VGCCs, voltage-gated K+ (KV) channels, large-conductance Ca2+-activated K+ (BKCa) channels, strong-inward-rectifier K+ (KIR) channels, ATP-sensitive K+ (KATP) channels, ryanodine receptors (RyRs), inositol 1,4,5-trisphosphate receptors (IP3Rs), and a variety of transient receptor potential (TRP) channels that contribute to pressure-induced myogenic tone in resistance arteries and arterioles, the modulation of the function of these ion channels by vasoconstrictors and vasodilators, their role in the functional regulation of tissue blood flow and their dysfunction in diseases such as hypertension, obesity, and diabetes.

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“…Ion channels in the membranes of endothelial cells contribute to all aspects of the function of these cells . Calcium influx and release through members of these membrane proteins determines intracellular Ca 2+ concentration.…”

Section: Introductionmentioning

confidence: 99%

“…Endothelial cells may express four or more classes of K + channels . The expression and function of strong inward rectifier K + (K IR 2.X) channels will be the focus of this review.…”

Section: Introductionmentioning

confidence: 99%

Boosting the signal: Endothelial inward rectifier K⁺ channels

Jackson

2017

Microcirculation

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Endothelial cells express a diverse array of ion channels including members of the strong inward rectifier family composed of KIR2 subunits. These two-membrane-spanning-domain channels are modulated by their lipid environment, and exist in macromolecular signaling complexes with receptors, protein kinases and other ion channels. Inward rectifier K+ channels (KIR) currents display a region of negative slope conductance at membrane potentials positive to the K+ equilibrium potential that allows outward current through the channels to be activated by membrane hyperpolarization, permitting KIR to amplify hyperpolarization induced by other K+ channels and ion transporters. Increases in extracellular K+ concentration activate KIR allowing them to sense extracellular K+ concentration and transduce this change into membrane hyperpolarization. These properties position KIR to participate in the mechanism of action of hyperpolarizing vasodilators and contribute to cell-cell conduction of hyperpolarization along the wall of microvessels. Expression of KIR in capillaries in electrically active tissues may allow KIR to sense extracellular K+, contributing to functional hyperemia. Understanding the regulation of expression and function of microvascular endothelial KIR will improve our understanding of the control of blood flow in the microcirculation in health and disease and may provide new targets for development of therapeutics in the future.

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Endothelial Cell Ion Channel Expression and Function in Arterioles and Resistance Arteries

Cited by 13 publications

References 185 publications

Electrical dynamics of isolated cerebral and skeletal muscle endothelial tubes: Differential roles of G‐protein‐coupled receptors and K⁺ channels

Electrical dynamics of isolated cerebral and skeletal muscle endothelial tubes: Differential roles of G‐protein‐coupled receptors and K⁺ channels

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Boosting the signal: Endothelial inward rectifier K⁺ channels

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Endothelial Cell Ion Channel Expression and Function in Arterioles and Resistance Arteries

Cited by 13 publications

References 185 publications

Electrical dynamics of isolated cerebral and skeletal muscle endothelial tubes: Differential roles of G‐protein‐coupled receptors and K+ channels

Electrical dynamics of isolated cerebral and skeletal muscle endothelial tubes: Differential roles of G‐protein‐coupled receptors and K+ channels

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Boosting the signal: Endothelial inward rectifier K+ channels

Contact Info

Product

Resources

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Electrical dynamics of isolated cerebral and skeletal muscle endothelial tubes: Differential roles of G‐protein‐coupled receptors and K⁺ channels

Electrical dynamics of isolated cerebral and skeletal muscle endothelial tubes: Differential roles of G‐protein‐coupled receptors and K⁺ channels

Boosting the signal: Endothelial inward rectifier K⁺ channels